SCIENCE SCREW-UP NO. 1

The Lophotrochozoa Ecdysozoa mistake

A big mistake in the tree of life – ignoring generation time

How it started

What should be one of the crowning jewels of achievement in molecular biology has been plagued by an unwarranted suggestion in an otherwise outstanding seminal paper (Zuckerkandl and Pauling, 1965) detailing the theory of molecular clocks.  They clearly laid out the factors determining genetic changes over time.  One of the factors was generation time of organisms.  They opined that it was impossible to determine the past generation times involved in the evolution of species, but that variation in generation time factors speeding and slowing rates would average out so generation time could be ignored.  The big mistake had its basis in this presumption.

Why it should have stopped

Within a few years, Kimura and Ohta (1971) noted that the pauling (a rate of substitution of ten to the minus nine per amino acid site per year) varied from one centipauling for histones to four paulings for fibrinopeptide A.  Of course the mutation rate for the nucleotides of DNA would be somewhat higher than 400-fold because of the redundancies in the DNA coding for amino acids. 

Laird, McConaughy, and McCarthy (1969) already had reported a ten-fold higher rate of nucleotide sequence variation for rodents compared to artiodactyls when time estimates were in years and said “This difference diminishes if generations, rather than years, represent the appropriate interval of evolutionary divergence.”  Britten (1986) noted that “Examination of available measurements shows that rates of DNA change of different phylogenetic groups differ by a factor of 5.”

Miyamoto, Sllghtom, and Goodman (1987) reported “. . the slowdown in the rate of sequence evolution evident in higher primates is especially pronounced in humans.”  Field et al. (1988) noted that “For distantly related organisms, it is not possible to establish homology between nucleotides in the rapidly evolving portions of the molecule; thus, even if the entire 18s rRNA sequence is known, only some parts of it can be used for phylogenetic inference.”

What should have stopped

Publication and acceptance by scientists in general of the Lophotrochozoa and Ecdysozoa; papers describing the Lophotrochozoa in 1995 (Halanych et al.), the Ecdysozoa in 1997 (Aguinaldo et al.), should have been rejected by peer review.  Both studies were based on 18S ribosomal DNA sequences.  Both run counter to results of classical phylogeny studies preceding molecular phylogenies; then the establishment accepts the contrary results of these two small samples although the authors noted several things that should have raised questions. 

For the 1995 Lophotrochozoa study, note 10 includes the following statement “Regions that could not be readily aligned were excluded from the analyses.”  And the 1997 Ecdysozoa paper says “It was unexpected to find nematodes contained within the Ecdysozoa because in previous molecular studies they diverged deep in the protostome tree, even before the deuterostome-protostome bifurcation.”  It seems that both reports were state of the art for molecular phylogeny studies of smaller evolutionary units having less variation in basic life cycles and molecular features.  So the problem is one of scale; errors are compounded when generation time is ignored.  The fact that small scale projections are not greatly affected must have made the authors and their peers think the new broad-scale studies were correct.  Big mistake.

It has been said that hindsight is 20/20

Sanderson (1996) would have shown them their sample size was too small.  Other alerts are now available from Maley and Marshall (1998), Martin and Palumbi (1993), Wägele (1999), and many others.  But with no correction for generation time in their algorithms, it was GIGO.  Computers can generate trees regardless of the quality of the input.  Unfortunately, the flawed results have been accepted and perpetuated in textbooks and additional research.

Disclaimer for conflict of interest

I admit to a certain amount of pique with both Nature and Science for having rejected manuscripts I submitted years ago that might have had a role in providing a better solution to the evolutionary tree of life.   I understand the need to reject over 90% of submissions means life is not necessarily fair for those seeking publication.  I made a 1988 presentation to the Michigan Academy entitled “A life cycle adjustment is needed for molecular clocks”.  In 2004 I presented “Ecdysozoa, Lophotrochozoa, and Other Molecular Phylogeny, Peer-Review Failures. “  The abstract was in the Michigan Academician, 36(1):118-119. I intended to submit the full paper to Science, but found their new submission rules beyond my digital capabilities.  More about the answers I have for evolutionary questions will be presented in future postings.   I might have accepted the Lophotrochozoa and Ecdysozoa proposal if I did not already have knowledge of a tree of life that better fits the facts; the pogonophorans provide critical information supporting the tree.

Joseph G. Engemann, Emeritus Professor of Biological Science, Western Michigan University,  Kalamazoo, MI   May 31, 2013

References cited

Aguinaldo, Anna Marie A., James M. Turbeville, Lawrence S. Linford, Maria C. Rivera, James R. Garey, Rudolf A. Raff, and James A. Lake.  1997.  Evidence for a clade of nematodes, arthropods and other moulting animals.  Nature, 387:489-493.

Britten, Roy J.  1986.  Rates of DNA sequence evolution differ between taxonomic groups.  Science, 231:1393-1398.  

Field, Katharine G., Gary J. Olsen, David J. Lane, Stephen J. Giovannoni, Michael T. Ghiselin, Elizabeth C. Raff, Norman R. Pace, and Rudolf A. Raff.  1988.  Molecular phylogeny of the animal kingdom.  Science, 239:748-753.

Halanych, Kenneth M., John D. Bacheller, Anna Marie A. Aguinaldo, Stephanie M. Liva, David M. Hillis, and James A. Lake.  1995.  Evidence from 18S ribosomal DNA that the lophophorates are protostome animals.  Science, 267:1641-1643. 

Kimura, Motoo, and Tomoko Ohta.  1971. On the rate of molecular evolution.  J. Molec. Evolution, 1:1-17.

Laird, Charles D., Betty L. McConaughy, and Brian J. McCarthy.  1969.  Rate of fixation of nucleotide substitutions in evolution.  Nature, 224:149-154.

Maley, Laura E., and Charles R. Marshall.  1998.  The coming of age of molecular systematics.  Science, 279:505-506. 

Martin, Andrew P., and Stephen R. Palumbi.  1993.  Body size, metabolic rate, generation time, and the molecular clock.  Proc. Natl. Acad. Sci. USA, 90:4087-4091.

Miyamoto, Michael M., Jerry L. Slightom, and Morris Goodman.  1987.  Phylogenetic relations of humans and African apes from DNA sequences in the ψη-globin region.  Science, 238:369-373.

Sanderson, Michael J.  1996.  How many taxa must be sampled to identify the root node of a large clade?  Syst. Biol., 45:168-173. 

Wägele, Johann-Wolfgang.  1999.  Major sources of errors in phylogenetic systematics.  Zool. Anz., 283:329-337. 

Zuckerkandl, Emile, and Linus Pauling.  1965.  Evolutionary divergence and convergence in proteins.  Pp. 97-166.  In: V. Bryson and H. J. Vogel (eds.).  Evolving Genes and Proteins.  Academic Press, N. Y.